Peptic ulcers include gastric ulcers, which occur as lesions in the wall of the stomach, and duodenal ulcers, which are deep lesions that occur in the wall of the duodenum, i.e., the upper portion of the small intestine. The body's main defense against the corrosive effects of potent gastric digestive juices is the mucous bicarbonate layer that lines the inside of the duodenum and stomach. Duodenal ulcers result from an imbalance in factors that maintain the natural mucous bicarbonate layer, thus leading to destruction of the epithelium and underlying connective tissues. Although current antiulcer therapeutics, including antisecretory products such as cimetidine and ranitidine, appear to be effective in healing duodenal ulcers, it is generally believed that they are effective because they reduce normal gastric acid secretion. While the reduction in acidity aids in the closure of the ulcer, it also interferes with normal digestion. Studies have shown that 40-60% of ulcers healed with current therapies recur within one year of therapy. The high rate of ulcer recurrence is thought to be at least partially attributable to the reduced number of mucus-producing cells in the scar tissue which is left at the site of the healed ulcer. This area is thus thought to be more vulnerable to rupture when the gastrointestinal acidity returns to normal.
Ulcerative colitis is an inflammatory bowel disease of the mucosal lining of the colon and rectum for which there is little effective treatment. It is a chronic debilitating disorder with high morbidity and can lead to colorectal cancer. The disease is for the most part confined to the mucosal and submucosal layers of the colonic wall, where severe inflammation of the colorectal mucosa, crypt abscesses and multiple ulcers occur. It is characterized by bloody stools, diarrhea, fever, and liver function abnormalities. More than 50% of all patients with chronic ulcerative colitis have surgery within the first two years of their illness to remove the affected tissues.
Ulcerative mucositis is a serious and dose-limiting toxic side effects of many forms of cancer chemotherapy. The lesions which occur as a consequence of this condition cause severe pain and loss of function in affected patients. The disruption in the oral mucosa results in a systemic portal of entry for the numerous microorganisms found in the mouth. Consequently, the oral cavity is the most frequently identifiable source of sepsis in the granulocytopenic cancer patient. Current therapy for mucositis is limited to either local or systemic palliation or topical antibacterial therapy.
PCT Application No. PCT/US89/03467 discloses the use of an acid-resistant fibroblast growth factor to treat GI ulcers.